Evolutionary Dynamics of Foot and Mouth Disease Virus Serotype A and Its Endemic Sub-Lineage A/ASIA/Iran-05/SIS-13 in Pakistan

Foot and mouth disease (FMD) causes severe economic losses to the livestock industry of endemic countries, including Pakistan. Pakistan is part of the endemic pool 3 for foot and mouth disease viruses (FMDV), characterized by co-circulating O, A, and Asia 1 serotypes, as designated by the world reference laboratory for FMD (WRL-FMD). FMDV serotype A lineage ASIA/Iran-05 is widespread in buffalos and cattle populations and was first reported in Pakistan in 2006. This lineage has a high turnover, with as many as 10 sub-lineages reported from Pakistan over the years. In this study, we reconstructed the evolutionary, demographic, and spatial history of serotype A and one of its sub-lineages, A/ASIA/Iran-05/SIS-13, prevalent in Pakistan. We sequenced nearly complete genomes of three isolates belonging to sub-lineage A/ASIA/Iran-05/SIS-13. We estimated recombination patterns and natural selection acting on the serotype A genomes. Source and transmission routes in Pakistan were inferred, and the clustering pattern of isolates of the SIS-13 sub-lineage were mapped on a tree. We hereby report nearly complete genome sequences of isolates belonging to sub-lineage A/ASIA/Iran-05/SIS-13, along with purported recombinant genomes, and highlight that complete coding sequences can better elucidate the endemic history and evolutionary pressures acting on long-term co-circulating FMDV strains.     

A late sharp increase in influenza detections and low interim vaccine effectiveness against the circulating A(H3N2) strain,Denmark, 2021/22 influenza season up to 25 March 2022

We estimated interim influenza A vaccine effectiveness (VE) following a late sharp rise in cases during an influenza A(H3N2)-dominated 2021/22 season, after lifting COVID-19 restrictions. In children aged 2–6 years offered a live attenuated influenza vaccine, adjusted VE was 62.7% (95% CI: 10.9–84.4) in hospitalised and 64.2% (95% CI: 50.5–74.1) in non-hospitalised children. In non-hospitalised patients aged 7–44 years, VE was 24.8% (95% CI: 12.8–35.2); VE was non-significant in remaining age groups and hospital/non-hospital settings.     

Uptake of Human Papillomavirus Vaccine and Intention to Vaccinate among Healthy Pregnant Women in Serbia: A Cross-Sectional Study on Awareness,Knowledge, and Attitudes

We aimed to assess awareness, knowledge, and attitudes of healthy pregnant women towards human papillomavirus (HPV), to estimate factors associated with a positive attitude towards HPV immunization and to assess the uptake of the vaccine among their children. A cross-sectional study was conducted at the University Clinic of Gynecology and Obstetrics, Belgrade, Serbia among pregnant women attending their regular gynecological check-ups at the 12th gestational week. Knowledge about HPV and HPV vaccine was assessed using a specifically designed 12-item and 5-item questionnaires. Out of total 265 included women, 79.3% had heard of HPV, and 37.5% knew that HPV vaccine exists. HPV vaccine knowledge score was associated with higher odds for a positive attitude towards vaccination of both female (OR = 4.10, 95% CI 1.50–11.29) and male (OR = 3.71, 95% CI 1.52–9.01) child. The number of children (OR = 1.32, 95% CI 1.04–1.67) and high vaccine knowledge score (OR = 1.64 95% CI 1.13–2.39) were independent predictors associated with willingness to vaccinate child against HPV. The gynecologist was the preferable point of reference for information seeking about the HPV vaccine. Despite relatively high HPV awareness and knowledge among pregnant women in Serbia, about one-third of them are HPV vaccine aware, and are willing to vaccinate their children against HPV.     

The genetic match between vaccine strains and circulating seasonal influenza A viruses in Vietnam, 2001–2009

Please cite this paper as: Vuong et al. (2013). The genetic match between vaccine strains and circulating seasonal influenza A viruses in Vietnam, 2001–2009. Influenza and Other Respiratory Viruses 7(6), 1151–1157. Background  Vietnam is currently developing domestic capability to manufacture influenza vaccines but information on the genetic and antigenic characteristics of locally circulating seasonal influenza viruses is limited. To assess the relevance of WHO recommended vaccine strains to the situation in Vietnam, we analyzed the genetic relatedness of the hemagglutinin (HA) gene of seasonal influenza A viruses circulating in Vietnam from 2001 to 2009 to WHO recommended vaccine strains over the same period. Methods and Principal findings  We sequenced the HA gene of 32 H1N1 and 44 H3N2 seasonal influenza A isolates from laboratory‐based sentinel surveillance sites in Hanoi from 2001 to 2005 and from a national influenza surveillance system from 2005 to 2009. H1 and H3 HA phylogenetic trees rooted to vaccine strains A/Beijing/295/1995 (H1N1) and A/Moscow/10/1999 (H3N2), respectively, were constructed with contemporary HA sequences of isolates from neighboring countries. We found some genetic differences between seasonal influenza H3N2 viruses and three WHO influenza vaccine strains recommended for use in the Northern and Southern Hemispheres for the 2001–2004 and 2007–2008 seasons and close genetic identity of circulating H3N2 strains with the recommended WHO Southern Hemisphere vaccine strains for 2004 and 2009 seasons. The genetic similarity of circulating H1N1 strains with the WHO recommended vaccine strains are described for the study period 2001–2009. Conclusions  The HA gene of seasonal influenza virus strains in Vietnam (especially influenza A/H3N2) showed varying degrees of genetic identity compared with those of the Northern or Southern Hemisphere vaccine strains recommended by WHO. The close relatedness of the HA of Vietnamese strains and contemporary strains from nearby countries indicate a good genetic match of circulating strains during study period. Greater representation of virus isolates from South East Asia in the vaccine strain selection process is desirable of influenza vaccine development in Vietnam.     

Effectiveness of COVID-19 vaccines against SARS-CoV-2 infection with the Delta (B.1.617.2) variant: second interim results of a living systematic review and meta-analysis, 1 January to 25 August 2021

The Delta variant has become the dominant strain of SARS-CoV-2. We summarised the evidence on COVID-19 vaccine effectiveness (VE) identified in 17 studies that investigated VE against different endpoints. Pooled VE was 63.1% (95% confidence interval (CI): 40.9–76.9) against asymptomatic infection, 75.7% (95% CI: 69.3–80.8) against symptomatic infection and 90.9% (95% CI: 84.5–94.7) against hospitalisation. Compared with the Alpha variant, VE against mild outcomes was reduced by 10–20%, but fully maintained against severe COVID-19.     

An Improved αvβ6-Receptor-Expressing Suspension Cell Line for Foot-and-Mouth Disease Vaccine Production

Foot-and-mouth disease (FMD) is endemic in large parts of sub-Saharan Africa, Asia and South America, where outbreaks in cloven-hooved livestock threaten food security and have severe economic impacts. Vaccination in endemic regions remains the most effective control strategy. Current FMD vaccines are produced from chemically inactivated foot-and-mouth disease virus (FMDV) grown in suspension cultures of baby hamster kidney 21 cells (BHK-21). Strain diversity means vaccines produced from one subtype may not fully protect against circulating disparate subtypes, necessitating the development of new vaccine strains that “antigenically match”. However, some viruses have proven difficult to adapt to cell culture, slowing the manufacturing process, reducing vaccine yield and limiting the availability of effective vaccines, as well as potentiating the selection of undesired antigenic changes. To circumvent the need to cell culture adapt FMDV, we have used a systematic approach to develop recombinant suspension BHK-21 that stably express the key FMDV receptor integrin αvβ6. We show that αvβ6 expression is retained at consistently high levels as a mixed cell population and as a clonal cell line. Following exposure to field strains of FMDV, these recombinant BHK-21 facilitated higher virus yields compared to both parental and control BHK-21, whilst demonstrating comparable growth kinetics. The presented data supports the application of these recombinant αvβ6-expressing BHK-21 in future FMD vaccine production.     

COVID-19 vaccine effectiveness against SARS-CoV-2 infection during the Delta period,a nationwide study adjusting for chance of exposure,the Netherlands,July to December 2021

BackgroundDifferential SARS-CoV-2 exposure between vaccinated and unvaccinated individuals may confound vaccine effectiveness (VE) estimates.AimWe conducted a test-negative case–control study to determine VE against SARS-CoV-2 infection and the presence of confounding by SARS-CoV-2 exposure.MethodsWe included adults tested for SARS-CoV-2 at community facilities between 4 July and 8 December 2021 (circulation period of the Delta variant). The VE against SARS-CoV-2 infection after primary vaccination with an mRNA (Comirnaty or Spikevax) or vector-based vaccine (Vaxzevria or Janssen) was calculated using logistic regression adjusting for age, sex and calendar week (Model 1). We additionally adjusted for comorbidity and education level (Model 2) and SARS-CoV-2 exposure (number of close contacts, visiting busy locations, household size, face mask wearing, contact with SARS-CoV-2 case; Model 3). We stratified by age, vaccine type and time since vaccination.ResultsVE against infection (Model 3) was 64% (95% CI: 50–73), only slightly lower than in Models 1 (68%; 95% CI: 58–76) and 2 (67%; 95% CI: 56–75). Estimates stratified by age group, vaccine and time since vaccination remained similar: mRNA VE (Model 3) among people ≥ 50 years decreased significantly (p = 0.01) from 81% (95% CI: 66–91) at < 120 days to 61% (95% CI: 22–80) at ≥ 120 days after vaccination. It decreased from 83% to 59% in Model 1 and from 81% to 56% in Model 2.ConclusionSARS-CoV-2 exposure did not majorly confound the estimated COVID-19 VE against infection, suggesting that VE can be estimated accurately using routinely collected data without exposure information.     

A recombinant herpes virus expressing influenza hemagglutinin confers protection and induces antibody-dependent cellular cytotoxicity

Despite widespread yearly vaccination, influenza leads to significant morbidity and mortality across the globe. To make a more broadly protective influenza vaccine, it may be necessary to elicit antibodies that can activate effector functions in immune cells, such as antibody-dependent cellular cytotoxicity (ADCC). There is growing evidence supporting the necessity for ADCC in protection against influenza and herpes simplex virus (HSV), among other infectious diseases. An HSV-2 strain lacking the essential glycoprotein D (gD), was used to create ΔgD-2, which is a highly protective vaccine against lethal HSV-1 and HSV-2 infection in mice. It also elicits high levels of IgG2c antibodies that bind FcγRIV, a receptor that activates ADCC. To make an ADCC-eliciting influenza vaccine, we cloned the hemagglutinin (HA) gene from an H1N1 influenza A strain into the ΔgD-2 HSV vector. Vaccination with ΔgD-2::HA_PR8 was protective against homologous influenza challenge and elicited an antibody response against HA that inhibits hemagglutination (HAI⁺), is predominantly IgG2c, strongly activates FcγRIV, and protects against influenza challenge following passive immunization of naïve mice. Prior exposure of mice to HSV-1, HSV-2, or a replication-defective HSV-2 vaccine (dl5-29) does not reduce protection against influenza by ΔgD-2::HA_PR8. This vaccine also continues to elicit protection against both HSV-1 and HSV-2, including high levels of IgG2c antibodies against HSV-2. Mice lacking the interferon-α/β receptor and mice lacking the interferon-γ receptor were also protected against influenza challenge by ΔgD-2::HA_PR8. Our results suggest that ΔgD-2 can be used as a vaccine vector against other pathogens, while also eliciting protective anti-HSV immunity.

Influenza remains a global health threat. Seasonal strains of influenza A and B cause an estimated 5 million cases of severe infections and 500,000 deaths per year (1). Influenza pandemics have caused even greater morbidity and mortality. During the H1N1 pandemic of 1918 to 1919, 500 million people, approximately one-third of the world’s population at that time, were estimated to have been infected with this strain, leading to 50 million deaths (2). The H1N1 pandemic of 2009 is estimated to have caused up to 575,000 deaths (2). Currently, three types of influenza vaccines are offered annually in the United States: a recombinant virus expressing influenza proteins, chemically inactivated virus, and live attenuated virus (3). Regardless of the vaccine type, multiple strains are included to increase the chances of developing sufficient protection against major circulating influenza strains. However, these vaccines primarily elicit a neutralizing antibody response that is sensitive to changes in the influenza virus due to antigenic drift and shift (4). Antigenic drift results from an accumulation of random mutations in influenza antigens, like hemagglutinin (HA), altering sites recognized by the immune system (4). Influenza A strains can also undergo antigenic shift, whereby two different influenza strains infect the same cell to form a reassortant virus with new antigenic properties (4). Due to limited immunity in the population, these new strains are highly virulent, causing widespread epidemics and disease (4). With antigenic drift and shift, vaccine-mediated protection against circulating strains has been insufficient (5). Influenza vaccines that elicit more robust and long-term protection are therefore needed. Notably, if an influenza vaccine with ≥75% efficacy were to be broadly used in the United States, an estimated 19,500 deaths a year could be prevented and direct healthcare costs reduced by $3.5 billion (6).For many years, efforts to improve influenza vaccines have focused on eliciting an immune response for full, broad protection against both circulating and future strains of the virus. These studies have shown that, in general, neutralizing antibodies are sufficient for homologous protection (7). However, achieving heterologous protection may require more broadly neutralizing antibodies or nonneutralizing antibodies able to activate effector immune cells (5). Previous studies have found that passively transferred nonneutralizing monoclonal antibodies can be potently protective in a mouse influenza challenge model (8–10). Several novel strategies have attempted to generate a nonneutralizing response against influenza. For example, vaccines have been created to specifically target the conserved stem region of HA (11–13).Nonneutralizing antibodies stimulate effector cell mechanisms, including antibody-mediated phagocytosis and antibody-dependent cellular cytotoxicity (ADCC), both of which require activation of the Fcγ receptors (FcγRs) (14). Specific isotypes of IgG antibodies are associated with FcγR modulation and subsequent ADCC activation, including the IgG1 and IgG3 subtypes in humans, as well as IgG2a and IgG2c subtypes in mice (15–19). IgG2a and IgG2c isotypes are functionally equivalent and mouse strain-dependent, with IgG2c present in C57BL/6J mice (20). Recent studies have demonstrated that natural infection by influenza and vaccination elicit nonneutralizing antibodies with effector functions that contribute to protection (5, 9, 21–27). In mouse and nonhuman primate challenge models, ADCC-mediating antibodies have demonstrated protection against both homologous and heterologous influenza challenge (9, 28).Recently, we developed a single-cycle herpes simplex virus (HSV) vaccine that completely protects against vaginal, skin, and ocular challenges by HSV-1 and HSV-2 (29, 30). Protection elicited by this vaccine, designated ΔgD-2 for its lack of the essential glycoprotein D (gD) gene, is transferable via passive infusion of immune sera to naïve wild-type mice but not to mice lacking the Fcγ common chain (30). The immune response elicited by ΔgD-2 primarily elicits nonneutralizing antibodies with high levels of FcγRIV-activating function.We asked whether ΔgD-2 could be used as a vaccine platform to induce broadly protective FcγRIV-activating antibodies against a heterologous antigen, such as influenza HA. In this study, we demonstrate that our recombinant vaccine, ΔgD-2::HA_PR8, elicits protection against influenza with a high proportion of FcγRIV-activating antibodies. Additionally, anticipating the use of ΔgD-2 as a vaccine vector against other pathogens, we tested whether our construct would still be protective in mice lacking interferon (IFN) function. Many humans have inborn errors in their IFN signaling pathways, leading to more lethal outcomes in infection (31). Patients with such deficiencies are disproportionately represented among HSV encephalitis cases and are often diagnosed only after presenting with serious symptoms (32–38). This at-risk population underscores the importance of eliciting protection against HSV in the absence of a functional IFN-α/β response. Additionally, many pathogens, such as dengue virus, require mouse models lacking IFN function, and for ease of testing, an efficacious vaccine should remain functional in these mice (39–41). In this study, we demonstrate that ΔgD-2 is a versatile, immunogenic vaccine vector that provides a strong FcγRIV-activating immune response against heterologous pathogens, while maintaining its protective benefit against HSV, in both wild-type and IFN-deficient mice.     

Prevalence of Neutralizing Antibodies to Canine Distemper Virus and Response to Vaccination in Client-Owned Adult Healthy Dogs

Re-vaccinations against canine distemper virus (CDV) are commonly performed in 3-year intervals. The study’s aims were to determine anti-CDV antibodies in healthy adult dogs within 28 days of vaccination against CDV, and to evaluate factors associated with the presence of pre-vaccination antibodies and with the antibody response to vaccination. Ninety-seven dogs, not vaccinated within 1 year before enrollment, were vaccinated with a modified live CDV vaccine. A measurement of the antibodies was performed before vaccination (day 0), on day 7, and 28 after the vaccination by virus neutralization. A response to vaccination was defined as a ≥4-fold titer increase by day 28. Fisher’s exact test was used to determine factors associated with a lack of antibodies and vaccination response. In total, 94.8% of the dogs (92/97; CI 95%: 88.2–98.1) had antibodies (≥10) prior to vaccination. A response to vaccination was not observed in any dog. Five dogs were considered humoral non-responders; these dogs neither had detectable antibodies before, nor developed antibodies after vaccination. Young age (<2 years) was significantly associated with a lack of pre-vaccination antibodies (p = 0.018; OR: 26.825; 95% CI: 1.216–1763.417). In conclusion, necessity of re-vaccination in adult healthy dogs should be debated and regular vaccinations should be replaced by antibody detection.     

Effectiveness of COVID-19 vaccines in preventing SARS-CoV-2 infection and hospitalisation,Navarre, Spain,January to April 2021

COVID-19 vaccine effectiveness was evaluated in close contacts of cases diagnosed during January–April 2021. Among 20,961 contacts, 7,240 SARS-CoV-2 infections were confirmed, with 5,467 being symptomatic and 559 leading to hospitalisations. Non-brand-specific one and two dose vaccine effectiveness were respectively, 35% (95% confidence interval (CI): 25 to 44) and 66% (95% CI: 57 to 74) against infections, 42% (95% CI: 31 to 52) and 82% (95% CI: 74 to 88) against symptomatic infection, and 72% (95% CI: 47 to 85) and 95% (95% CI: 62 to 99) against COVID-19 hospitalisation. The second dose significantly increased effectiveness. Findings support continuing complete vaccination.     

Asia1型口蹄疫新型多表位疫苗免疫豚鼠的效力试验

目的 评价一种改进型Asia 1型口蹄疫多表位重组疫苗的免疫效能。方法 根据Asia 1型口蹄疫病毒的基因序列设计多表位基因,构建重组表达质粒(pRE-oIgG)。用大肠杆菌细胞分别表达靶标蛋白RE-oIgG和口蹄疫病毒3D蛋白,并用组氨酸亲和层析柱纯化。纯化的RE-oIgG,3D和RE-oIgG与3D的混合物分别经油性佐剂IAS206乳化后配制成相应的疫苗。25只雌性豚鼠被随机分成5组,每组5只豚鼠,经肌肉途径分别注射RE-oIgG、3D、RE-oIgG与3D的混合物、Asia 1口蹄疫灭活疫苗和PBS,所有动物进行两次免疫。采用ELISA、病毒微量中和试验、攻毒试验和流式细胞术分别测定免疫前后抗口蹄疫特异性抗体、中和抗体、保护率以及淋巴细胞增殖反应。结果 RE-oIgG与3D的混合物能够诱导高效价的抗Asia 1型口蹄疫病毒的特异性抗体,与RE-oIgG单独免疫豚鼠相比较具有明显的差异性(P<0.05)。除了阴性对照组PBS外,来自所有免疫动物的外周血淋巴细胞经过体外培养刺激后均产生了明显的淋巴细胞增殖反应。单独免疫3D蛋白和安慰剂PBS实验组既没有测到抗口蹄疫病毒特异性抗体,也没有测到中和抗体。而RE-oIgG与3D的混合物不仅诱导机体产生了高水平的保护性中和抗体,而且诱发了明显的淋巴细胞增殖反应。更为重要的是,该蛋白质混合物针对1 000 GPID₅₀强毒攻击后,所有动物没有出现症状完全保护。值得一提的是,单独免疫3D蛋白的5只豚鼠中,其中2只完全保护;另外3只虽然出现了临床症状,但相对PBS对照组来说发病时间大约推迟2～3 d。因此,笔者认为RE-oIgG与3D的混合物不仅能够诱导体液免疫反应,而且能够诱发细胞免疫反应,是一种高效能的新型疫苗,将来可用于我国口蹄疫的防控。     

Vaccine effectiveness against SARS-CoV-2 transmission to household contacts during dominance of Delta variant (B.1.617.2), the Netherlands,August to September 2021

We estimated SARS-CoV-2 vaccine effectiveness against onward transmission by comparing secondary attack rates among household members for vaccinated and unvaccinated index cases, based on source and contact tracing data collected when the Delta variant was dominant. Effectiveness of full vaccination of the index case against transmission to unvaccinated and fully vaccinated household contacts, respectively, was 63% (95% confidence interval (CI): 46–75) and 40% (95% CI: 20–54), in addition to the direct protection of vaccination of contacts against infection.     

Live‐attenuated influenza vaccine effectiveness against hospitalization in children aged 2–6 years,the first three seasons of the childhood influenza vaccination program in England, 2013/14–2015/16

IntroductionIn 2013, the United Kingdom began to roll‐out a universal annual influenza vaccination program for children. An important component of any new vaccination program is measuring its effectiveness. Live‐attenuated influenza vaccines (LAIVs) have since shown mixed results with vaccine effectiveness (VE) varying across seasons and countries elsewhere. This study aims to assess the effectiveness of influenza vaccination in children against severe disease during the first three seasons of the LAIV program in England.MethodsUsing the screening method, LAIV vaccination coverage in children hospitalized with laboratory‐confirmed influenza infection was compared with vaccination coverage in 2–6‐year‐olds in the general population to estimate VE in 2013/14–2015/16.ResultsThe overall LAIV VE, adjusted for age group, week/month and geographical area, for all influenza types pooled over the three influenza seasons was 50.1% (95% confidence interval [CI] 31.2, 63.8). By age, there was evidence of protection against hospitalization from influenza vaccination in both the pre‐school (2–4‐year‐olds) (48.1%, 95% CI 27.2, 63.1) and school‐aged children (5–6‐year‐olds) (62.6%, 95% CI 2.6, 85.6) over the three seasons.ConclusionLAIV vaccination in children provided moderate annual protection against laboratory‐confirmed influenza‐related hospitalization in England over the three influenza seasons. This study contributes further to the limited literature to date on influenza VE against severe disease in children.     

Vaccine effectiveness against symptomatic SARS-CoV-2 infection in adults aged 65 years and older in primary care: I-MOVE-COVID-19 project,Europe, December 2020 to May 2021

We measured COVID-19 vaccine effectiveness (VE) against symptomatic SARS-CoV-2 infection at primary care/outpatient level among adults ≥ 65 years old using a multicentre test-negative design in eight European countries. We included 592 SARS-CoV-2 cases and 4,372 test-negative controls in the main analysis. The VE was 62% (95% CI: 45–74) for one dose only and 89% (95% CI: 79–94) for complete vaccination. COVID-19 vaccines provide good protection against COVID-19 presentation at primary care/outpatient level, particularly among fully vaccinated individuals.     

Deliberate reduction of hemagglutinin and neuraminidase expression of influenza virus leads to an ultraprotective live vaccine in mice

A long-held dogma posits that strong presentation to the immune system of the dominant influenza virus glycoprotein antigens neuraminidase (NA) and hemagglutinin (HA) is paramount for inducing protective immunity against influenza virus infection. We have deliberately violated this dogma by constructing a recombinant influenza virus strain of A/PR8/34 (H1N1) in which expression of NA and HA genes was suppressed. We down-regulated NA and HA expression by recoding the respective genes with suboptimal codon pair bias, thereby introducing hundreds of nucleotide changes while preserving their codon use and protein sequence. The variants PR8-NA^Min, PR8-HA^Min, and PR8-(NA+HA)^Min (Min, minimal expression) were used to assess the contribution of reduced glycoprotein expression to growth in tissue culture and pathogenesis in BALB/c mice. All three variants proliferated in Madin–Darby canine kidney cells to nearly the degree as WT PR8. In mice, however, they expressed explicit attenuation phenotypes, as revealed by their LD₅₀ values: PR8, 32 plaque-forming units (PFU); HA^Min, 1.7 × 10³ PFU; NA^Min, 2.4 × 10⁵ PFU; (NA+HA)^Min, ≥3.16 × 10⁶ PFU. Remarkably, (NA+HA)^Min was attenuated >100,000-fold, with NA^Min the major contributor to attenuation. In vaccinated mice (NA+HA)^Min was highly effective in providing long-lasting protective immunity against lethal WT challenge at a median protective dose (PD₅₀) of 2.4 PFU. Moreover, at a PD₅₀ of only 147 or 237, (NA+HA)^Min conferred protection against heterologous lethal challenges with two mouse-adapted H3N2 viruses. We conclude that the suppression of HA and NA is a unique strategy in live vaccine development.     

Vaccine effectiveness against severe acute respiratory infections (SARI) COVID-19 hospitalisations estimated from real-world surveillance data,Slovenia, October 2021

We estimated vaccine effectiveness (VE) against severe COVID-19 during October 2021, using Slovenian surveillance data. For people fully vaccinated with any vaccine in age groups 18–49, 50–64, ≥ 65 years, VE was 86% (95% CI: 79–90), 89% (85–91), and 77% (74–81). Among ≥ 65 year-olds fully vaccinated with mRNA vaccines, VE decreased from 93% (95% CI: 88–96) in those vaccinated ≤ 3 months ago to 43% (95% CI: 30–54) in those vaccinated ≥ 6 months ago, suggesting the need for early boosters.     

Immune Response 5–7 Months after Vaccination against SARS-CoV-2 in Elderly Nursing Home Residents in the Czech Republic: Comparison of Three Vaccines

Background and Aims: Elderly nursing home residents are especially prone to a severe course of SARS-CoV-2 infection. In this study, we aimed to investigate the complex immune response after vaccination depending on the convalescence status and vaccine. Methods: Sampling took place in September–October 2021. IgG antibodies against spike protein and nucleocapsid protein, the titer of virus neutralization antibodies against delta and (on a subset of patients) omicron, and cellular immunity (interferon-gamma release assay) were tested in nursing home residents vaccinated with Pfizer, Moderna (both 30–31 weeks after the completion of vaccination), or AstraZeneca (23 weeks) vaccines. The prevalence with 95% confidence intervals (CI) was evaluated in Stata version 17. Results: 95.2% (95% CI: 92.5–97.1%) of the 375 participants had positive results of anti-S IgG, 92.8% (95% CI: 89.7–95.2%) were positive in virus neutralization assay against delta, and 89.0% (95% CI: 84.5–92.5%) in the interferon-gamma-releasing assay detecting cellular immunity. Results of the virus neutralization assay against omicron correlated with those against delta but the neutralization capacity was reduced by about half. As expected, the worst results were found for the AstraZeneca vaccine, although the vaccination-to-test period was the shortest for this vaccine. All immune parameters were significantly higher in convalescent residents than in naive residents after vaccination. No case of COVID-19 occurred during the vaccination-to-test period. Conclusions: A high immune response, especially among vaccinated convalescents (i.e., residents with hybrid immunity), was found in elderly nursing home residents 5–7 months after vaccination against SARS-CoV-2. In view of this, it appears that such residents are much better protected from COVID-19 than those who are only vaccinated and the matter of individual approach to the booster dose in such individuals should be further discussed.     

Spotlight influenza: Estimation of influenza vaccine effectiveness in elderly people with assessment of residual confounding by negative control outcomes,Finland, 2012/13 to 2019/20

BackgroundCohort studies on vaccine effectiveness are prone to confounding bias if the distribution of risk factors is unbalanced between vaccinated and unvaccinated study subjects.AimWe aimed to estimate influenza vaccine effectiveness in the elderly population in Finland by controlling for a sufficient set of confounders based on routinely available register data.MethodsFor each of the eight consecutive influenza seasons from 2012/13 through 2019/20, we conducted a cohort study comparing the hazards of laboratory-confirmed influenza in vaccinated and unvaccinated people aged 65–100 years using individual-level medical and demographic data. Vaccine effectiveness was estimated as 1 minus the hazard ratio adjusted for the confounders age, sex, vaccination history, nights hospitalised in the past and presence of underlying chronic conditions. To assess the adequacy of the selected set of confounders, we estimated hazard ratios of off-season hospitalisation for acute respiratory infection as a negative control outcome.ResultsEach analysed cohort comprised around 1 million subjects, of whom 37% to 49% were vaccinated. Vaccine effectiveness against laboratory-confirmed influenza ranged from 16% (95% confidence interval (CI): 12–19) to 48% (95% CI: 41–54). More than 80% of the laboratory-confirmed cases were hospitalised. The adjusted off-season hazard ratio estimates varied between 1.00 (95% CI: 0.94–1.05) and 1.08 (95% CI: 1.01–1.15), indicating that residual confounding was absent or negligible.ConclusionSeasonal influenza vaccination reduces the hazard of severe influenza disease in vaccinated elderly people. Data about age, sex, vaccination history and utilisation of hospital care proved sufficient to control confounding.     

Comparative safety, immunogenicity, and efficacy of several anti-H5N1 influenza experimental vaccines in a mouse and chicken models (Testing of killed and live H5 vaccine)

Please cite this paper as: Gambaryan et al. (2011) Comparative safety, immunogenicity, and efficacy of several anti‐H5N1 influenza experimental vaccines in a mouse and chicken models. Parallel testing of killed and live H5 vaccine. Influenza and Other Respiratory Viruses 6(3), 188–195. Objective Parallel testing of inactivated (split and whole virion) and live vaccine was conducted to compare the immunogenicity and protective efficacy against homologous and heterosubtypic challenge by H5N1 highly pathogenic avian influenza virus. Method Four experimental live vaccines based on two H5N1 influenza virus strains were tested; two of them had hemagglutinin (HA) of A/Vietnam/1203/04 strain lacking the polybasic HA cleavage site, and two others had hemagglutinins from attenuated H5N1 virus A/Chicken/Kurgan/3/05, with amino acid substitutions of Asp54/Asn and Lys222/Thr in HA1 and Val48/Ile and Lys131/Thr in HA2 while maintaining the polybasic HA cleavage site. The neuraminidase and non‐glycoprotein genes of the experimental live vaccines were from H2N2 cold‐adapted master strain A/Leningrad/134/17/57 (VN‐Len and Ku‐Len) or from the apathogenic H6N2 virus A/Gull/Moscow/3100/2006 (VN‐Gull and Ku‐Gull). Inactivated H5N1 and H1N1 and live H1N1 vaccine were used for comparison. All vaccines were applied in a single dose. Safety, immunogenicity, and protectivity against the challenge with HPAI H5N1 virus A/Chicken/Kurgan/3/05 were estimated. Results All experimental live H5 vaccines tested were apathogenic as determined by weight loss and conferred more than 90% protection against lethal challenge with A/Chicken/Kurgan/3/05 infection. Inactivated H1N1 vaccine in mice offered no protection against challenge with H5N1 virus, while live cold‐adapted H1N1 vaccine reduced the mortality near to zero level. Conclusions The high yield, safety, and protectivity of VN‐Len and Ku‐Len made them promising strains for the production of inactivated and live vaccines against H5N1 viruses.     

Effectiveness of the Comirnaty (BNT162b2, BioNTech/Pfizer) vaccine in preventing SARS-CoV-2 infection among healthcare workers,Treviso province,Veneto region,Italy, 27 December 2020 to 24 March 2021

Data on effectiveness of the BioNTech­/Pfizer COVID-19 vaccine in real-world settings are limited. In a study of 6,423 healthcare workers in Treviso Province, Italy, we estimated that, within the time intervals of 14–21 days from the first and at least 7 days from the second dose, vaccine effectiveness in preventing SARS-CoV-2 infection was 84% (95% confidence interval (CI): 40–96) and 95% (95% CI: 62–99), respectively. These results could support the ongoing vaccination campaigns by providing evidence for targeted communication.